The pentapeptide QYNAD does not block voltage-gated sodium channels

T. R. Cummins, M. Renganathan, P. K. Stys, R. I. Herzog, K. Scarfo, R. Horn, S. D. Dib-Hajj, S. G. Waxman

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background: An endogenous pentapeptide (Gln-Tyr-Asn-Ala-Asp; QYNAD) that is present at elevated levels in human CSF from patients with demyelinating diseases has been reported to block voltage-gated sodium channels at low (10 μM) concentrations. Objective: Because of the potential importance of sodium channel blocking activity in demyelinating disorders, this study attempted to determine the sensitivity to QYNAD of different sodium channel subtypes, including Navl.6, the major sodium channel at nodes of Ranvier, and Nav1.2, which is expressed in axons with abnormal myelin. Methods: Sodium channel function was assayed using patch-clamp recordings, both in heterologous expression systems and in intact neurons. Results: QYNAD synthesized in 10 different batches by four different facilities failed to block sodium currents, even at concentrations as high as 500 μM (50-fold higher than the blocking concentration originally reported). QYNAD had no effect on the currents produced by recombinant Nav1.2, Nav1.4, Nav1.6, and Nav1.7 sodium channels or on the sodium currents that are produced by native channels in adult hippocampal or dorsal root ganglion neurons. QYNAD did not interfere with conduction in the optic nerve, a myelinated fiber tract that is often affected in MS. Conclusions: These experiments do not show any sodium channel blocking effect of QYNAD. The conclusion that QYNAD contributes to the pathophysiology of inflammatory neurologic disorders by blocking voltage-gated sodium channels should therefore be viewed with caution.

Original languageEnglish (US)
Pages (from-to)224-229
Number of pages6
JournalNeurology
Volume60
Issue number2
DOIs
StatePublished - Jan 28 2003
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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    Cummins, T. R., Renganathan, M., Stys, P. K., Herzog, R. I., Scarfo, K., Horn, R., Dib-Hajj, S. D., & Waxman, S. G. (2003). The pentapeptide QYNAD does not block voltage-gated sodium channels. Neurology, 60(2), 224-229. https://doi.org/10.1212/01.WNL.0000042423.36650.BD